WO2024120483A1 - Utilisation d'un composé de quinoléine pour le traitement du cancer de l'ovaire - Google Patents

Utilisation d'un composé de quinoléine pour le traitement du cancer de l'ovaire Download PDF

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WO2024120483A1
WO2024120483A1 PCT/CN2023/137081 CN2023137081W WO2024120483A1 WO 2024120483 A1 WO2024120483 A1 WO 2024120483A1 CN 2023137081 W CN2023137081 W CN 2023137081W WO 2024120483 A1 WO2024120483 A1 WO 2024120483A1
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WIPO (PCT)
Prior art keywords
ovarian cancer
pharmaceutically acceptable
compound
formula
acceptable salt
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PCT/CN2023/137081
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English (en)
Chinese (zh)
Inventor
万晓婧
张喜全
王训强
于鼎
朱名洁
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正大天晴药业集团股份有限公司
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Publication of WO2024120483A1 publication Critical patent/WO2024120483A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4

Definitions

  • the present invention belongs to the field of medical technology, and relates to the use of quinoline compounds in treating ovarian cancer, and specifically to the use and method of N-(4-((7-((1-(cyclopentylamino)cyclopropane)methoxy)-6-methoxyquinoline-4-yl)oxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide in treating ovarian cancer.
  • Ovarian cancer is a malignant tumor that occurs in ovarian tissue and is one of the common malignant tumors of the female reproductive system. Its incidence rate is second only to cervical cancer and endometrial cancer, but its mortality rate ranks first, posing a serious threat to women's health.
  • WO2012034055 discloses N-(4-((7-((1-(cyclopentylamino)cyclopropanyl)methoxy)-6-methoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (hereinafter referred to as the compound of formula (I)) as a c-Met kinase inhibitor and its use in inhibiting tyrosine kinase activity.
  • the compound of formula (I) is a new class of compounds with excellent pharmacological properties, which can inhibit the activity of multiple protein tyrosine kinases, such as c-Met, VEGFr, EGFr, c-kit, PDGF, FGF, SRC, Ron, Tie2, etc.
  • multiple protein tyrosine kinases such as c-Met, VEGFr, EGFr, c-kit, PDGF, FGF, SRC, Ron, Tie2, etc.
  • the present disclosure provides a compound of formula (I) or a pharmaceutically acceptable salt thereof for use in treating ovarian cancer.
  • the present disclosure provides use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating ovarian cancer.
  • the present disclosure provides use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in treating ovarian cancer.
  • the present disclosure provides a method for treating ovarian cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the present disclosure provides a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof for treating ovarian cancer.
  • the pharmaceutical composition further contains a pharmaceutically acceptable excipient.
  • the present disclosure provides the use of a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating ovarian cancer.
  • the pharmaceutical composition is a pharmaceutical composition in a single-dose form, or a pharmaceutical composition in a multi-dose form.
  • the pharmaceutical composition further contains a pharmaceutically acceptable excipient.
  • the present disclosure provides use of a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof in treating ovarian cancer.
  • the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.
  • the present disclosure provides a method for treating ovarian cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.
  • the present disclosure provides a kit for treating ovarian cancer, the kit comprising: a) a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof; and b) a method for treating ovarian cancer.
  • the kit may contain a single dose or multiple doses of a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the ovarian cancer includes epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer.
  • the ovarian cancer is selected from epithelial ovarian cancer.
  • the epithelial ovarian cancer is selected from serous carcinoma, endometrial carcinoma, clear cell carcinoma, and mucinous carcinoma.
  • the epithelial ovarian cancer is a serous carcinoma.
  • the serous carcinoma includes low-grade serous carcinoma (LGSC) and high-grade serous carcinoma (HGSC).
  • LGSC low-grade serous carcinoma
  • HGSC high-grade serous carcinoma
  • the ovarian cancer patient is initially diagnosed with a serous carcinoma, such as an invasive low-grade serous carcinoma.
  • the ovarian cancer is inoperable ovarian cancer.
  • the ovarian cancer is recurrent ovarian cancer.
  • the ovarian cancer is metastatic ovarian cancer.
  • the ovarian cancer is advanced ovarian cancer.
  • the ovarian cancer is ovarian cancer that has previously received at least one systemic therapy.
  • the ovarian cancer is ovarian cancer that has previously received at least one systemic therapy and has failed treatment (eg, progressed or recurred after treatment).
  • the ovarian cancer is ovarian cancer that has been previously treated with one or two systemic therapies.
  • the ovarian cancer is ovarian cancer that has previously received one or two systemic therapies and has failed treatment (eg, progressed or recurred after treatment).
  • the ovarian cancer is ovarian cancer that has been previously treated with at least two systemic therapies.
  • the ovarian cancer is ovarian cancer that has previously received at least two systemic therapies and has failed treatment (eg, progressed or recurred after treatment).
  • the ovarian cancer is ovarian cancer that has previously received greater than or equal to first-line systemic treatment.
  • the ovarian cancer is ovarian cancer that has previously received at least one line of systemic therapy and has failed treatment (eg, progressed or recurred after treatment).
  • the ovarian cancer is ovarian cancer that has previously received first-line, second-line, third-line, fourth-line, or fifth-line systemic treatment.
  • the ovarian cancer is ovarian cancer that has previously received first-line, second-line, third-line, fourth-line, or fifth-line systemic treatment and has failed treatment (eg, progressed or relapsed after treatment).
  • the systemic therapy is selected from targeted therapy or systemic chemotherapy.
  • the targeted therapy drug is selected from PARP inhibitors.
  • the PARP inhibitors include but are not limited to pamiparib, fozoparib, niraparib, talazoparib, rucaparib, olaparib, senaparib, and veliparib.
  • the PARP inhibitor is selected from olaparib, niraparib, fozoparib, and pamiparib.
  • the ovarian cancer is ovarian cancer that has been previously treated with at least one systemic chemotherapy.
  • the ovarian cancer is ovarian cancer that has previously received at least one systemic chemotherapy and has failed treatment (eg, progressed or recurred after treatment).
  • the ovarian cancer is ovarian cancer that has been previously treated with one or two systemic chemotherapies.
  • the ovarian cancer is ovarian cancer that has previously received one or two systemic chemotherapies and has failed treatment (eg, progressed or recurred after treatment).
  • the ovarian cancer is ovarian cancer that has been previously treated with at least two lines of systemic chemotherapy.
  • the ovarian cancer is ovarian cancer that has been previously treated with at least two systemic chemotherapies and has failed treatment (eg, progressed or relapsed after treatment).
  • the ovarian cancer is ovarian cancer that has previously received greater than or equal to first-line systemic treatment.
  • the ovarian cancer is ovarian cancer that has previously received first-line, second-line, third-line, fourth-line, or fifth-line systemic treatment.
  • the ovarian cancer is ovarian cancer that has previously received a line of systemic treatment.
  • the ovarian cancer is ovarian cancer that has previously received at least one line of systemic therapy and has failed treatment (eg, progressed or recurred after treatment).
  • the ovarian cancer is ovarian cancer that has previously received two lines of systemic treatment.
  • the ovarian cancer is ovarian cancer that has previously received at least two lines of systemic therapy and has failed treatment (eg, progressed or relapsed after treatment).
  • the ovarian cancer is ovarian cancer that has previously received three lines of systemic treatment.
  • the ovarian cancer is ovarian cancer that has previously received at least three lines of systemic treatment and has failed treatment (eg, progressed or relapsed after treatment).
  • the systemic chemotherapy drugs include but are not limited to one or more of the following: alkylating agents (including but not limited to bendamustine, carmustine, chlorambucil, nitrogen mustard, lomustine, carboplatin, cisplatin, oxaliplatin, cyclophosphamide, ifosfamide, dacarbazine, temozolomide); antimetabolites (including but not limited to azacitidine, cytarabine, 5-fluorouracil, leucovorin, 6-mercaptopurine, capecitabine, decitabine, gemcitabine, floxuridine, fludarabine, nelarabine, hydroxyurea, methotrexate, pralatrexate, pemetrexed, pentostatin, hexamethylmelamine, trifluridine/decitabine); and combinations of vinorelbine); plant alkaloids (including but not limited to camptothecin and vinorelbine); antitum
  • the systemic chemotherapy drugs include but are not limited to one or more of platinum drugs, fluoropyrimidine derivatives, camptothecins, taxanes, vinca alkaloids, anthracyclines, antibiotics, podophyllums, other anti-tumor drugs, and anti-metabolites.
  • examples include, but are not limited to, one or more of the following: platinum drugs (e.g., oxaliplatin, miplatin, cisplatin, carboplatin, nedaplatin, dicycloplatin, lobaplatin, triplatin tetranitrate, phenaplatin, picoplatin, satraplatin, lobaplatin), fluoropyrimidine derivatives (e.g., gemcitabine, capecitabine, ancitabine, fluorouracil, bifurouracil, doxifluridine, tegafur, carmofur, trifluridine), taxanes (e.g., paclitaxel, albumin-bound paclitaxel, and docetaxel), camptothecins (e.g., camptothecin, hydroxycamptothecin, 9-aminocamptothecin, 7-ethylcamptothecin, irinotecan, topotecan), vinca
  • the systemic chemotherapy drug is selected from one or more of carboplatin, cisplatin, oxaliplatin, doxorubicin (including liposome doxorubicin, doxorubicin hydrochloride), paclitaxel, albumin-bound paclitaxel, docetaxel, bleomycin, etoposide, gemcitabine, 5-fluorouracil, leucovorin, topotecan, altretamine, capecitabine, ifosfamide, irinotecan, pemetrexed, and vinorelbine.
  • the systemic chemotherapy drug is selected from paclitaxel + carboplatin, paclitaxel + cisplatin, carboplatin + liposomal doxorubicin, docetaxel + carboplatin, bleomycin + etoposide + cisplatin, etoposide + carboplatin, gemcitabine + carboplatin, gemcitabine + cisplatin, carboplatin + albumin-bound paclitaxel, 5-fluorouracil + leucovorin + oxaliplatin, capecitabine + oxaliplatin, liposomal doxorubicin, docetaxel, albumin-bound paclitaxel, etoposide, gemcitabine, paclitaxel, topotecan, altretamine, capecitabine, ifosfamide, irinotecan, pemetrexed, oxaliplatin, or vinorelbine.
  • the systemic chemotherapy drug is selected from paclitaxel + carboplatin, paclitaxel + cisplatin, doxorubicin (e.g., doxorubicin hydrochloride) + carboplatin or cisplatin, carboplatin + liposomal doxorubicin, docetaxel + carboplatin, docetaxel + cisplatin, bleomycin + etoposide + cisplatin, etoposide + carboplatin, gemcitabine + carboplatin, gemcitabine + cisplatin, carboplatin + albumin-bound paclitaxel, 5-fluorouracil + leucovorin + oxaliplatin, capecitabine + oxaliplatin, liposomal doxorubicin, docetaxel, albumin-bound paclitaxel, etoposide, gemcitabine, paclitaxel, topotecan, altretamine, cap
  • the ovarian cancer is ovarian cancer that has previously received a systemic chemotherapy and has failed treatment
  • the drug of the systemic chemotherapy is selected from doxorubicin (e.g., doxorubicin hydrochloride) + carboplatin or cisplatin, doxorubicin liposome + carboplatin, paclitaxel + carboplatin, paclitaxel + cisplatin, docetaxel + carboplatin, docetaxel + cisplatin, bleomycin + etoposide + cisplatin, or etoposide + carboplatin.
  • doxorubicin e.g., doxorubicin hydrochloride
  • doxorubicin liposome + carboplatin paclitaxel + carboplatin
  • paclitaxel + carboplatin paclitaxel + cisplatin
  • docetaxel + carboplatin docetaxel + cisplatin
  • the ovarian cancer is ovarian cancer that has previously received a systemic chemotherapy and failed treatment
  • the drug of the systemic chemotherapy is selected from doxorubicin liposome + carboplatin, paclitaxel + carboplatin, paclitaxel + cisplatin, docetaxel + carboplatin, bleomycin + etoposide + cisplatin, or etoposide + carboplatin.
  • the ovarian cancer is ovarian cancer that has previously received and failed a systemic chemotherapy, wherein the systemic chemotherapy drug is selected from a combination of a platinum drug and a taxane drug.
  • the platinum drug includes but is not limited to one or more of cisplatin, carboplatin, nedaplatin, oxaliplatin, miplatin, dicycloplatin, picoplatin, satraplatin, phenaplatin, tetranitrotriplaplatin or lobaplatin.
  • the taxanes include, but are not limited to, one or more of paclitaxel, nab-paclitaxel, or docetaxel.
  • the combination of the platinum drug and the taxane drug is selected from paclitaxel + carboplatin, paclitaxel + cisplatin, docetaxel + carboplatin, docetaxel + cisplatin, albumin-bound paclitaxel + carboplatin, or albumin-bound paclitaxel + cisplatin.
  • the ovarian cancer is ovarian cancer that has been previously treated with a systemic chemotherapy and failed to be treated, and the drug of the systemic chemotherapy is selected from a combination of platinum drugs and anthracyclines.
  • the platinum drugs include but are not limited to one or more of cisplatin, carboplatin, nedaplatin, oxaliplatin, miplatin, bicycloplatin, picoplatin, satraplatin, pheniplatin, tetranitrotriplaton or lobaplatin.
  • the anthracycline includes doxorubicin, such as liposomal doxorubicin and doxorubicin hydrochloride.
  • the ovarian cancer is ovarian cancer that has previously received two systemic chemotherapy treatments and failed to respond, wherein the systemic chemotherapy drugs include a combination of a platinum drug and a taxane drug and a combination of a platinum drug and an anthracycline drug.
  • the ovarian cancer is ovarian cancer that has previously received two systemic chemotherapy and failed treatment; wherein the first systemic chemotherapy drug is selected from a combination of platinum drugs and taxane drugs; the second systemic chemotherapy drug is selected from a combination of platinum drugs and anthracycline drugs.
  • the platinum drugs include but are not limited to one or more of cisplatin, carboplatin, nedaplatin, oxaliplatin, miplatin, bicycloplatin, picoplatin, satraplatin, pheniplatin, tetranitrotriplatin or lobaplatin.
  • the taxane drugs include but are not limited to one or more of paclitaxel, albumin-bound paclitaxel or docetaxel.
  • the anthracycline drugs include doxorubicin, such as liposomal doxorubicin and doxorubicin hydrochloride.
  • the ovarian cancer is ovarian cancer that has been previously treated with two or more systemic chemotherapy and has failed treatment
  • the systemic chemotherapy drugs include a combination of a platinum drug and a taxane drug and a combination of a platinum drug and anthracycline drug.
  • the ovarian cancer is ovarian cancer that has been previously treated with two or more systemic chemotherapy and has failed treatment; wherein the first systemic chemotherapy drug is selected from a combination of a platinum drug and a taxane drug; the second systemic chemotherapy drug is selected from a combination of a platinum drug and an anthracycline drug; for the third or more systemic chemotherapy drugs, they can be selected from a combination of different platinum drugs and taxane drugs, and a combination of different platinum drugs and anthracycline drugs.
  • the platinum drugs include but are not limited to one or more of cisplatin, carboplatin, nedaplatin, oxaliplatin, miplatin, bicycloplatin, picoplatin, satraplatin, pheniplatin, tetranitrotriplatin or lobaplatin.
  • the taxane drugs include but are not limited to one or more of paclitaxel, albumin-bound paclitaxel or docetaxel.
  • the anthracycline drugs include doxorubicin, such as doxorubicin liposomes and doxorubicin hydrochloride.
  • the ovarian cancer is ovarian cancer that has previously received two systemic chemotherapy treatments and failed; wherein the first systemic chemotherapy drug is selected from doxorubicin liposome + carboplatin, paclitaxel + carboplatin, paclitaxel + cisplatin, docetaxel + carboplatin, bleomycin + etoposide + cisplatin, or etoposide + carboplatin; the second systemic chemotherapy drug is selected from paclitaxel + carboplatin, docetaxel + carboplatin, carboplatin + gemcitabine, carboplatin + doxorubicin liposome, cisplatin + gemcitabine, carboplatin + albumin-bound paclitaxel, 5-fluorouracil + leucovorin + oxaliplatin, capecitabine + oxaliplatin, doxorubicin liposome, docetaxel, albumin-bound paclitaxel, etopo
  • the ovarian cancer is ovarian cancer that has been previously treated with at least one line of systemic therapy and has failed treatment, and the drug of the first-line systemic therapy is selected from a combination of a platinum drug and a taxane drug.
  • the ovarian cancer is ovarian cancer that has been previously treated with at least one line of systemic therapy and failed, and the drug for the first-line systemic therapy is selected from docetaxel + cisplatin or carboplatin, or paclitaxel + carboplatin or cisplatin.
  • the ovarian cancer is ovarian cancer that has been previously treated with at least two lines of systemic therapy and failed, and the drug for the second-line systemic therapy is selected from a combination of platinum drugs and taxane drugs.
  • the ovarian cancer is ovarian cancer that has previously received at least two lines of systemic treatment and failed treatment
  • the second-line systemic treatment drug is selected from docetaxel + cisplatin or carboplatin, or paclitaxel + carboplatin or cisplatin.
  • the ovarian cancer is ovarian cancer that has previously received at least three lines of systemic treatment and failed treatment, and the drugs used in the third-line systemic treatment are selected from a combination of platinum drugs and anthracycline drugs.
  • the ovarian cancer is ovarian cancer that has previously received at least three lines of systemic treatment and failed treatment
  • the third-line systemic treatment drug is selected from doxorubicin (eg, doxorubicin hydrochloride) + carboplatin or cisplatin.
  • the ovarian cancer is ovarian cancer that has been previously treated with at least four lines of systemic therapy and has failed treatment, and the drugs of the fourth-line systemic therapy are selected from a combination of platinum drugs and taxane drugs.
  • the ovarian cancer is ovarian cancer that has been previously treated with at least four lines of systemic therapy and has failed treatment, and the drugs of the fourth-line systemic therapy are selected from docetaxel + cisplatin or carboplatin.
  • the ovarian cancer patient has not been treated with anti-angiogenic drugs.
  • the anti-angiogenic drug comprises pazopanib, sorafenib, erlotinib, apatinib, cabozantinib, anlotinib, recombinant human endostatin, or bevacizumab.
  • the ovarian cancer patient has not received anti-angiogenic drug treatment, and the anti-angiogenic drug includes apatinib, cabozantinib, anlotinib, recombinant human endostatin, or bevacizumab.
  • the ovarian cancer patient has not received anti-angiogenic drug treatment, and the anti-angiogenic drug includes cabozantinib, anlotinib, recombinant human endostatin, or bevacizumab.
  • the anti-angiogenic drug comprises apatinib or bevacizumab.
  • the patient with ovarian cancer has previously received surgical treatment.
  • the ovarian cancer patient has previously received surgical treatment and has failed treatment (eg, has progressed or relapsed after treatment).
  • the ovarian cancer patient has previously received targeted therapy, wherein the targeted therapy drug is selected from PARP inhibitors.
  • the ovarian cancer patient is a patient with advanced ovarian cancer
  • the ovarian cancer is selected from epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
  • the patient has previously received at least two systemic chemotherapy treatments and has failed the treatment.
  • the ovarian cancer patient has undergone one surgical treatment and three chemotherapy treatments in sequence but all treatments have failed.
  • the ovarian cancer patient has undergone surgery but failed, two paclitaxel + carboplatin treatments but failed, and doxorubicin + carboplatin treatment but failed.
  • the ovarian cancer patient has undergone one chemotherapy, one surgical treatment, and three chemotherapy treatments in sequence but all failed.
  • the ovarian cancer patient has sequentially undergone docetaxel + cisplatin treatment but treatment failure, surgical treatment but treatment failure, docetaxel + cisplatin treatment but treatment failure, doxorubicin hydrochloride + carboplatin treatment but treatment failure, and docetaxel + carboplatin treatment but treatment failure.
  • the ovarian cancer patient meets all of the following conditions:
  • the ovarian cancer patient is an advanced ovarian cancer patient
  • the ovarian cancer is selected from epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
  • the patient has previously received at least two systemic chemotherapy treatments and failed, and has not received anti-angiogenic drug treatment.
  • the ovarian cancer patient meets all of the following conditions:
  • the administration cycle of the compound of formula (I) or its pharmaceutically acceptable salt is 2-6 weeks. In some embodiments, the administration cycle of the compound of formula (I) or its pharmaceutically acceptable salt is 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks or the range formed by any of the above values. In some embodiments, the administration cycle of the compound of formula (I) or its pharmaceutically acceptable salt is 3 weeks or 4 weeks.
  • the administration cycle of the compound of formula (I) or its pharmaceutically acceptable salt may be more than 1 administration cycle, including 1, 2, 3, 4, 5, 6 or more administration cycles. In some embodiments, the administration cycle of the compound of formula (I) or its pharmaceutically acceptable salt may preferably be 1-6 administration cycles.
  • the frequency of administration of the compound of formula (I) or a pharmaceutically acceptable salt thereof can be 3 times a day, 2 times a day, or 1 time a day. In some embodiments, the administration frequency of the compound of formula (I) or its pharmaceutically acceptable salt is 3 times a day, 2 times a day or 1 time a day. In some embodiments, the administration frequency of the compound of formula (I) or its pharmaceutically acceptable salt is 1 time a day.
  • the daily dose of the compound of formula (I) or a pharmaceutically acceptable salt thereof is 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, or a range formed by any of the above values.
  • the daily dose of the compound of formula (I) or its pharmaceutically acceptable salt is selected from 20-180 mg. In some embodiments, the daily dose of the compound of formula (I) or its pharmaceutically acceptable salt is selected from 20-40 mg, 20-60 mg, 20-90 mg, 20-120 mg, 20-150 mg, 40-60 mg, 40-90 mg, 40-120 mg, 40-150 mg, 40-180 mg, 60-90 mg, 60-120 mg, 60-150 mg, 60-180 mg, 90-120 mg, 90-150 mg, 90-180 mg, 120-150 mg, 120-180 mg or 150-180 mg.
  • the daily dose of the compound of formula (I) or a pharmaceutically acceptable salt thereof is selected from 60-120 mg, 60-150 mg, 60-180 mg, 90-120 mg, 90-150 mg, 90-180 mg, 120-150 mg, 120-180 mg or 150-180 mg.
  • the daily dose of the compound of formula (I) or its pharmaceutically acceptable salt is selected from 60 mg, 90 mg, 120 mg, 150 mg or 180 mg. In some embodiments, the daily dose of the compound of formula (I) or its pharmaceutically acceptable salt is selected from 90 mg or 120 mg.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered in the form of a pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof is administered in a single dose or multiple doses. In some embodiments, it is administered in multiple doses.
  • the pharmaceutical composition is a pharmaceutical composition with a single dose of 30-60 mg of a compound of formula (I) or a pharmaceutically acceptable salt thereof. In some embodiments, the pharmaceutical composition is a pharmaceutical composition with a single dose of 30 mg or 60 mg of a compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the pharmaceutical composition is a multiple-dose pharmaceutical composition of a compound of formula (I) or a pharmaceutically acceptable salt thereof, and the multiple doses may consist of a single dose of 30 mg or 60 mg of a compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the pharmaceutical composition is a pharmaceutical composition of multiple doses of a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein the multiple doses of a compound of formula (I) or a pharmaceutically acceptable salt thereof may be 60 mg, 90 mg, 120 mg, 150 mg or 180 mg. In some embodiments, the multiple doses of a compound of formula (I) or a pharmaceutically acceptable salt thereof are 90 mg or 120 mg.
  • the multiple doses of the pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof may consist of a single dose of 30 mg or 60 mg of the pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof is administered as follows: a daily dose of 60 mg, 90 mg, 120 mg, 150 mg or 180 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered for one or more dosing cycles.
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition is administered as follows: a daily dose of 60 mg, 90 mg, 120 mg, 150 mg or 180 mg of the compound of formula (I) or its pharmaceutically acceptable salt is administered for one or more dosing cycles, and the frequency of administration may be 3 times a day, 2 times a day, once a day, once every two days, once every three days, once every four days, once every five days, once every six days, 3 times a week, 2 times a week, once a week, once every two weeks, or once every three weeks, preferably 3 times a day, 2 times a day or once a day.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof is administered as follows: a daily dose of 60 mg, 90 mg, 120 mg, 150 mg or 180 mg of a compound of formula (I) or a pharmaceutically acceptable salt thereof is administered to a subject for one or more dosing cycles, and the administration is continued every day (e.g., 3 times a day, 2 times a day or once a day).
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition is administered as follows: a daily dose of 60 mg, 90 mg, 120 mg, 150 mg or 180 mg of the compound of formula (I) or its pharmaceutically acceptable salt is administered to the subject continuously every day (e.g., 3 times a day, 2 times a day or once a day).
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition is administered as follows: with a 28-day administration cycle, a daily dose of 60 mg, 90 mg, 120 mg, 150 mg or 180 mg, administered once a day.
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition is administered as follows: one or more administration cycles are administered with 28 days as one administration cycle, and the daily dose is 60 mg, 90 mg, 120 mg, 150 mg or 180 mg, administered once a day.
  • the daily dose of the compound of formula (I) or a pharmaceutically acceptable salt thereof is selected from 60 mg, 90 mg, 120 mg, 150 mg or 180 mg, optionally, the daily dose can be adjusted after administration (including but not limited to upward or downward adjustment of the daily dose).
  • the daily dose of the compound of formula (I) or a pharmaceutically acceptable salt thereof is selected from 90 mg or 120 mg.
  • the daily dose is adjusted after administration (including but not limited to upward or downward adjustment of the daily dose).
  • the daily dose of the compound of formula (I) or its pharmaceutically acceptable salt may be 90 mg or 120 mg, and optionally, the daily dose is adjusted upward after administration. In some embodiments, the daily dose of the compound of formula (I) or its pharmaceutically acceptable salt may be 90 mg or 120 mg, and optionally, the daily dose is adjusted upward after administration to a daily dose selected from 120 mg, 150 mg or 180 mg.
  • the daily dose of the compound of formula (I) or its pharmaceutically acceptable salt is selected from 90 mg or 120 mg, and optionally, the daily dose is adjusted downward after administration. In some embodiments, the daily dose of the compound of formula (I) or its pharmaceutically acceptable salt is selected from 90 mg, and optionally, the daily dose is adjusted downward after administration to 60 mg or less. In some embodiments, the daily dose of the compound of formula (I) or its pharmaceutically acceptable salt is selected from 120 mg, and optionally, the daily dose is adjusted downward after administration to 90 mg or 60 mg or less.
  • the daily dose of the compound of formula (I) or its pharmaceutically acceptable salt is selected from 90 mg, and optionally, the daily dose is adjusted down to 60 mg after administration. In some embodiments, the daily dose of the compound of formula (I) or its pharmaceutically acceptable salt is selected from 120 mg, and optionally, the daily dose is adjusted down to 90 mg or 60 mg after administration.
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition can be administered by various routes, including but not limited to oral administration.
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition can be taken orally on an empty stomach (e.g., in the morning on an empty stomach).
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition is administered by oral administration on an empty stomach in the morning, once a day, for one or more dosing cycles (for example, 28 days can be one dosing cycle).
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition is administered by oral administration on an empty stomach in the morning, once a day, for one or more dosing cycles, wherein 28 days is one dosing cycle.
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition is administered as follows: oral administration on an empty stomach every day (e.g., once a day), with a daily dose of 60 mg, 90 mg, 120 mg, 150 mg or 180 mg, for one or more consecutive administration cycles (e.g., 28 days as one administration cycle).
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition is administered as follows: with a dosing cycle of 28 days, it is orally administered once a day on an empty stomach, with a daily dose of 60 mg, 90 mg, 120 mg, 150 mg or 180 mg, for 28 consecutive days (i.e., one dosing cycle).
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition is administered as follows: with a dosing cycle of 28 days, orally administered once a day on an empty stomach, with each dose of 60 mg, 90 mg, 120 mg, 150 mg or 180 mg, for 28 consecutive days (i.e., one dosing cycle).
  • the above dosing cycle is repeated as long as the disease remains under control and the regimen is clinically tolerated.
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition is prepared in a single or multiple dose form suitable for each administration of 60 mg-180 mg, or 60 mg-150 mg, or 60 mg-120 mg, or 90 mg-180 mg, or 90 mg-150 mg, or 90 mg-120 mg, or 120 mg-150 mg, or 120 mg-180 mg, or 150 mg-180 mg, or 60 mg, or 90 mg, or 120 mg, or 150 mg, or 180 mg of the compound of formula (I) or its pharmaceutically acceptable salt.
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition is prepared in a single or multiple dose form suitable for once a day and administering 60mg-180mg, or 60mg-150mg, or 60mg-120mg, or 90mg-180mg, or 90mg-150mg, or 90mg-120mg, or 120mg-150mg, or 120mg-180mg, or 150mg-180mg, or 60mg, or 90mg, or 120mg, or 150mg, or 180mg of the compound of formula (I) or its pharmaceutically acceptable salt to the patient each time.
  • the compound of formula (I) or its pharmaceutically acceptable salt or its pharmaceutical composition is prepared in a single or multiple dose form suitable for administering 60 mg-180 mg, or 60 mg-150 mg, or 60 mg-120 mg, or 90 mg-180 mg, or 90 mg-150 mg, or 90 mg-120 mg, or 120 mg-150 mg, or 120 mg-180 mg, or 150 mg-180 mg, or 60 mg, or 90 mg, or 120 mg, or 150 mg, or 180 mg of the compound of formula (I) or its pharmaceutically acceptable salt once a day for 28 consecutive days.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof of the present disclosure is used as a single active agent.
  • the compounds of formula (I) disclosed herein can be administered in the form of their free base or in the form of their pharmaceutically acceptable salts.
  • pharmaceutically acceptable salts of the compounds of formula (I) can be prepared from various organic and inorganic acids according to methods known in the art.
  • the inorganic acid can be selected from hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid or phosphoric acid
  • the organic acid can be selected from succinic acid, maleic acid, acetic acid, fumaric acid, citric acid, tartaric acid, benzoic acid, p-toluenesulfonic acid, methanesulfonic acid or naphthylsulfuric acid.
  • the compound of formula (I) is administered in the form of its free base.
  • the "compound of formula (I) or a pharmaceutically acceptable salt thereof” described in the present disclosure may be in the form of a “pharmaceutical composition of the compound of formula (I) or a pharmaceutically acceptable salt thereof".
  • the method of administration can be determined comprehensively based on the activity, toxicity and patient tolerance of the drug.
  • the pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof further comprises a pharmaceutically acceptable excipient.
  • a pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof may be suitable for oral administration.
  • the pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof is a solid pharmaceutical composition.
  • the solid pharmaceutical composition is a capsule.
  • the pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof is a capsule formulation with strengths of 30 mg and 60 mg.
  • the pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof is a capsule preparation, which comprises the compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
  • the pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof is a capsule preparation comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof, corn starch, carboxymethylcellulose calcium, hypromellose and magnesium stearate.
  • the pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof is a capsule preparation, which comprises the compound of formula (I) or a pharmaceutically acceptable salt thereof, lactose, microcrystalline cellulose, sodium starch glycolate and magnesium stearate.
  • the compound of formula (I) or its pharmaceutically acceptable salt, or its pharmaceutical composition disclosed herein has good safety and anti-tumor activity, shows good inhibitory activity against ovarian cancer cells, and shows good tumor inhibition activity in a human ovarian tumor subcutaneous transplanted tumor model in nude mice.
  • the treatment scheme disclosed in the present invention has good efficacy and good safety in the treatment of ovarian cancer.
  • the compound of formula (I) or its pharmaceutically acceptable salt, or a pharmaceutical composition comprising the compound of formula (I) or its pharmaceutically acceptable salt at least in survival efficacy evaluation, such as overall survival (OS), median survival; in tumor response efficacy evaluation, such as disease-free survival (DFS), median DFS, progression-free survival (PFS), 6-month PFS rate, time to disease progression (TTP), objective response rate (ORR), disease control rate (DCR), duration of remission (DOR); and tolerance or safety evaluation, such as the incidence and severity of adverse events, etc., at least one aspect has excellent effect.
  • survival efficacy evaluation such as overall survival (OS), median survival
  • tumor response efficacy evaluation such as disease-free survival (DFS), median DFS, progression-free survival (PFS), 6-month PFS rate, time to disease progression (TTP), objective response rate (ORR), disease control rate (DCR), duration of remission (
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof has a good objective response rate and/or disease control rate in the treatment of ovarian cancer.
  • the dosages and ranges thereof provided herein relating to the compound of formula (I) or its pharmaceutically acceptable salt are calculated based on the molecular weight of the free base of the compound of formula (I).
  • paclitaxel + carboplatin indicates the combined use of paclitaxel and carboplatin.
  • pharmaceutically acceptable refers to those compounds, materials, compositions and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response or other problems or complications, commensurate with a reasonable benefit/risk ratio.
  • pharmaceutically acceptable salt includes salts formed by alkali ions and free acids (free acid) or salts formed by acid ions and free bases (free alkali).
  • treatment generally refers to obtaining a desired pharmacological and/or physiological effect, including partial or complete stabilization or cure of a disease and/or effects resulting from a disease.
  • treatment encompasses any treatment of a patient's disease, including: (a) suppressing the symptoms of the disease, i.e., preventing its development; or (b) relieving the symptoms of the disease, i.e., causing regression of the disease or symptoms.
  • first-line systemic therapy refers to the first treatment given to a disease. It is usually part of a group of standard treatments, such as surgery followed by chemotherapy and radiation therapy. When used alone, first-line therapy is generally considered the best treatment. If it does not cure the disease or causes serious side effects, other treatments may be added or used.
  • second-line systemic therapy refers to treatment given when the initial treatment (first-line treatment) is ineffective or stops working. The same applies to third-line treatment or more lines of treatment.
  • treatment failure refers to disease progression, recurrence, or intolerable side effects during or after treatment.
  • recurrent cancer is a cancer that has recurred at the original site or at a distant site after responding to initial treatment (eg, surgery).
  • an effective amount means an amount of a compound of the present disclosure that (i) treats a particular disease, condition or disorder, or (ii) alleviates, ameliorates or eliminates one or more symptoms of a particular disease, condition or disorder.
  • the amount of active substance e.g., a compound of the present disclosure
  • a “therapeutically effective amount” varies depending on the compound, the disease state and its severity, the mode of administration, and the age of the subject (e.g., a mammal) to be treated, but can be routinely determined by those skilled in the art based on their own knowledge and the present disclosure.
  • administering means physically introducing a composition comprising an active compound into a host or patient or subject using any of a variety of methods and delivery systems known to those skilled in the art. In certain embodiments, administration is oral.
  • daily dose refers to the dose administered to a patient for one day.
  • patient or subject or subject are used interchangeably herein to refer to mammals, such as humans, dogs, cows, horses, pigs, sheep, goats, cats, mice, rabbits, rats, and transgenic non-human animals.
  • the patient or subject or subject is a human.
  • single dose refers to the smallest packaging unit containing a certain amount of medicine. For example, if a box of medicine contains seven capsules, each capsule is a single dose; for example, if a box of medicine contains seven tablets, each tablet is a single dose.
  • multiple doses consists of a plurality of single doses.
  • composition refers to a mixture of one or more active ingredients of the present disclosure and pharmaceutically acceptable excipients.
  • the purpose of a pharmaceutical composition is to facilitate administration of a compound of the present disclosure to a subject.
  • pharmaceutically acceptable excipients refers to those excipients that have no significant irritation to the organism and do not impair the biological activity and performance of the active compound. Suitable excipients are well known to those skilled in the art, such as carbohydrates, waxes, water-soluble and/or water-swellable polymers, hydrophilic or hydrophobic materials, gelatin, oils, solvents, water, etc.
  • the pharmaceutical composition of the present disclosure can be prepared by combining the compound of the present application with suitable pharmaceutically acceptable excipients, for example, it can be formulated into a solid preparation (e.g., granules, tablets, pills, capsules, etc.), or formulated into a liquid preparation (e.g., injection).
  • suitable pharmaceutically acceptable excipients for example, it can be formulated into a solid preparation (e.g., granules, tablets, pills, capsules, etc.), or formulated into a liquid preparation (e.g., injection).
  • the pharmaceutical composition of the present disclosure can be manufactured by methods well known in the art, such as conventional mixing methods, dissolving methods, granulating methods, making dragees, grinding methods, emulsifying methods, freeze-drying methods, and the like.
  • Solid oral compositions can be prepared by conventional mixing, filling or tableting methods. For example, they can be obtained by mixing the active compound with a solid excipient, optionally grinding the resulting mixture, adding other suitable excipients if necessary, and then processing the mixture into particles to obtain the core of a capsule, tablet or dragee.
  • suitable excipients include, but are not limited to, adhesives, diluents, disintegrants, lubricants, glidants, sweeteners or flavoring agents, etc.
  • day When referring to a dosing regimen, the terms "day,” “daily,” and the like refer to the times within a calendar day, beginning at midnight and ending at the following midnight.
  • OVCAR3 cells Take OVCAR3 cells in good growth state, collect them into centrifuge tubes, adjust the cell density to 5 ⁇ 10 4 cells/mL, inoculate them on 96-well plates (100 ⁇ L/well), culture them in a cell culture incubator overnight, use a nanoliter sampler to add compounds, and make the final concentration of the compounds 10000nM-4.57nM, 2 replicates, and set up controls at the same time.
  • the detection reagent CCK-8 manufactured by adding the detection reagent CCK-8 (manufacturer
  • the cells were incubated in a cell culture incubator for 4 hours, and the absorbance was measured at 450 nm using an Envision microplate reader. Four-parameter analysis was performed, and the dose-effect curve was fitted to calculate the IC 50 .
  • the compounds of formula (I) disclosed herein exhibit good inhibitory activity against ovarian cancer cells.
  • OVCAR3 cells were subcutaneously inoculated in the right axilla of SPF female nude mice (source: Jiangsu Huachuang Xinnuo Pharmaceutical Technology Co., Ltd.), 1 ⁇ 10 7 cells/mouse. When the average tumor volume reached about 150 mm 3 , the animals were divided into groups.
  • the day of grouping was day 0. From day 0 onwards, drugs were administered by gavage once a day. Tumor volume was measured 2-3 times a week, and the mice were weighed and the data were recorded. The general performance of the mice was observed and recorded daily. After the experiment, the tumor was removed, weighed, and photographed.
  • the detection indicators and calculation formula are as follows:
  • Tumor volume, TV (mm 3 ) 1/2 ⁇ (a ⁇ b 2 ); where a is the long diameter of the tumor, and b is the short diameter of the tumor.
  • T/C (%) TRTV / CRTV ⁇ 100%, wherein TRTV is the RTV of the treatment group; CRTV is the RTV of the vehicle control group.
  • TGI (%) (1-TW/TW 0 ) ⁇ 100%; wherein, TW is the tumor weight of the treatment group, and TW 0 is the tumor weight of the vehicle control group.
  • Body weight change rate, WCR (%) (Wt t - Wt 0 )/Wt 0 ⁇ 100%; wherein Wt 0 is the body weight of mice on day 0, and Wt t is the body weight of mice at each measurement.
  • the compound of formula (I) disclosed in the present invention exhibits good tumor inhibition activity in a human ovarian tumor subcutaneous transplantation tumor model in nude mice.
  • Female subjects of childbearing age should agree to use contraceptive measures (such as intrauterine devices, birth control pills or condoms) during the study and within 6 months after the end of the study; the serum pregnancy test should be negative within 7 days before study entry, and the subjects must be non-breastfeeding; male subjects should agree to use contraceptive measures during the study and within 6 months after the end of the study.
  • contraceptive measures such as intrauterine devices, birth control pills or condoms
  • Test drug capsules of compound of formula (I), specifications: 30 mg or 60 mg.
  • Dosage method Oral administration on an empty stomach in the morning, once a day, for 28 consecutive days as a cycle, until the study termination criteria are met.
  • Dosage 90mg or 120mg.
  • Effectiveness evaluation RECIST 1.1 standard was used for evaluation.
  • AEs adverse events
  • SAEs serious adverse events
  • TEAEs treatment-emergent adverse events
  • Objective response rate refers to the proportion of subjects whose tumor volume reduction reaches the predetermined value and can be maintained for the minimum time limit according to the RECIST 1.1 standard, that is, the proportion of subjects with complete remission (CR) and partial remission (PR).
  • Progression-free survival refers to the time from the first treatment to the first disease progression or death due to any reason, whichever occurs first, regardless of whether the subject stopped the study treatment before the disease progressed, but re-acceptance of other approved systemic anticancer treatments is not included. If the subject has no disease progression and has not died, lost to follow-up, or received other systemic anticancer treatments by the data analysis cutoff date, the data will be treated as censored data, and the censoring date will be the date of the last imaging examination of the measurable lesions. If the subject has missed more than 3 RECIST assessment visits before the disease progresses or dies, the censoring date will be the date of the last imaging examination of the last measurable lesion before that. The PFS time was always based on the imaging examination date, not the assessment date or visit date.
  • DCR Disease control rate
  • Duration of response refers to the time from the first evaluation of complete response or partial response of the tumor to the first disease progression or death from various causes. If the tumor response is not confirmed, it will not be used. If the patient does not have disease progression or death from various causes before the data analysis cutoff date, it will be treated as censored data, and the PFS censoring time will be used to determine the duration of response.
  • OS Overall survival
  • the test results show that the compound of formula (I) disclosed in the present invention has good safety, can effectively control the progression of the disease, and shows certain clinical benefits.
  • the disease was effectively controlled by using the treatment regimen of the compound of formula (I) disclosed in the present invention; in a patient with advanced ovarian cancer whose disease progressed after docetaxel + cisplatin, surgical treatment, docetaxel + cisplatin, doxorubicin hydrochloride + carboplatin, and docetaxel + carboplatin treatment, the disease was effectively controlled by using the treatment regimen of the compound of formula (I) disclosed in the present invention.

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Abstract

La présente invention concerne l'utilisation d'un composé de quinoléine pour le traitement du cancer de l'ovaire, et concerne spécifiquement l'utilisation et un procédé de N-(4-((7-((1-(cyclopentylamino)cyclopropanyl)méthoxy)-6-méthoxyquinolin-4-yl)oxy)-3-fluorophényl)-N-(4-fluorophényl)cyclopropane-1,1-dicarboxamide pour le traitement du cancer de l'ovaire.
PCT/CN2023/137081 2022-12-08 2023-12-07 Utilisation d'un composé de quinoléine pour le traitement du cancer de l'ovaire WO2024120483A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103328447A (zh) * 2010-09-12 2013-09-25 南京爱德程医药科技有限公司 作为c-Met激酶抑制剂的化合物
WO2019166012A1 (fr) * 2018-03-02 2019-09-06 正大天晴药业集团股份有限公司 Cristal d'un composé à utiliser en tant qu'inhibiteur de kinase c-met, son procédé de préparation et son utilisation
WO2021185234A1 (fr) * 2020-03-16 2021-09-23 正大天晴药业集团股份有限公司 Composition pharmaceutique combinée de composé en tant qu'inhibiteur de kinase c-met et son utilisation
WO2021244551A1 (fr) * 2020-06-02 2021-12-09 正大天晴药业集团股份有限公司 Composition pharmaceutique combinée d'inhibiteur de kinase c-met et d'anticorps anti-pd-l1
WO2022111618A1 (fr) * 2020-11-26 2022-06-02 正大天晴药业集团股份有限公司 Composition pharmaceutique combinée d'un anticorps anti-pd-l1 et d'un inhibiteur de la kinase c-met pour le traitement du cancer du poumon

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103328447A (zh) * 2010-09-12 2013-09-25 南京爱德程医药科技有限公司 作为c-Met激酶抑制剂的化合物
WO2019166012A1 (fr) * 2018-03-02 2019-09-06 正大天晴药业集团股份有限公司 Cristal d'un composé à utiliser en tant qu'inhibiteur de kinase c-met, son procédé de préparation et son utilisation
WO2021185234A1 (fr) * 2020-03-16 2021-09-23 正大天晴药业集团股份有限公司 Composition pharmaceutique combinée de composé en tant qu'inhibiteur de kinase c-met et son utilisation
WO2021244551A1 (fr) * 2020-06-02 2021-12-09 正大天晴药业集团股份有限公司 Composition pharmaceutique combinée d'inhibiteur de kinase c-met et d'anticorps anti-pd-l1
WO2022111618A1 (fr) * 2020-11-26 2022-06-02 正大天晴药业集团股份有限公司 Composition pharmaceutique combinée d'un anticorps anti-pd-l1 et d'un inhibiteur de la kinase c-met pour le traitement du cancer du poumon

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